Tay-Sachs disease is a lysosomal storage disorder caused by mutation of the gene encoding the alpha chain of beta-hexosaminidase A. Cultured fibroblasts derived from some patients fail to synthesize any protein corresponding to the alpha chain, whereas those of others synthesize cross-reactive material (CRM) that does not form competent enzyme. Previously, we have shown that fibroblasts of late infantile Tay-Sachs patients of Ashkenazi origin are CRM-negative due to absence of functional mRNA. We have cloned a cDNA fragment corresponding to the alpha chain and shown absence of mRNA by Northern blot analysis in cells of such patients. Isolation and sequencing of full-length cDNA and of genome clones has been undertaken to determine the precise nature of the mutation. Similar studies have been undertaken with the beta chain of beta-hexosaminidase; cells of several patients with beta chain defects (Sandhoff disease) have likewise shown the existence of CRM-positive and CRM-negative mutations. In collaboration with investigators at NICHD, a protocol has been initiated to test the clinical value of amnion implants in the treatment of mucopolysaccharide storage disorders. The rationale is that the implants would provide lysosomal enzymes to the recipients. Preliminary results include subjective changes reported by parents but not change in serum or leukocyte enzyme levels.